Currently, there is no consensus regarding optimal front-line treatment for younger high-risk patients with large B cell lymphoma. American recommendations list only R-CHOP as standard, while ...European also include R-ACVBP and R-CHOEP14. We have been routinely using the latter regimen at our institution since 2011 and performed this retrospective real-life single-center study to analyze outcomes. Between September 2011 and April 2019, 66 newly diagnosed patients aged 18 to 60 years with B-large cell lymphoma and high-risk age-adjusted International Prognostic Index score were scheduled to receive 6 or 8 cycles of bi-weekly chemoimmunotherapy with cyclophosphamide, doxorubicin, vincristine, etoposide, steroids, and rituximab (R-CHOEP14). After a median follow-up of 4.7 years, the estimated 3-year progression-free survival was 87% (95% CI 80–96%) and 3-year overall survival 90% (95% CI 83–98%). Grade ≥ 3 hematological side effects occurred in 83% and infectious in 41% of patients; one patient died of toxicity. Grade ≥ 2 cardiac toxicity occurred in 21% of patients, more frequently than previously reported. The cumulative 5-year risk of congestive heart failure with all-cause mortality as the competing risk was 17%. R-CHOEP14 is a very effective and manageable regimen for younger high-risk patients with B-large cell lymphoma, but the risk of cardiotoxicity warrants further investigations.
Chronic kidney dysfunction is associated with increased mortality in multiple cancer types. Preliminary evidence suggests the same to be true for B-large cell lymphomas (B-LCL). To analyze the ...relationship of glomerular filtration rate (GFR) and outcome of B-LCL in detail we collected data on outcomes of 285 consecutive patients with newly diagnosed B-LCL treated at our institution with standard rituximab-containing regimens who did not have preexisting kidney disease or urinary tract obstruction at presentation. Median age was 59, range 18 to 87, 145 were male and 140 females. Forty-four had GFR < 60 mL/min, 123 had 60 to 90 mL/min, and 118 > 90 mL/min. Median follow-up of surviving patients was 49 months and estimated 3-year survival 76%. In univariate analysis age (P < .001), GFR (P = .014), stage (P < .001), performance status (P = .044), chemotherapy regimen (P < .01), and international prognostic index (IPI) (P < .001) were statistically significant prognostic factors. In multivariate analysis, age and GFR remained the only independent prognostic factors. Subtracting 1 from the IPI score of patients who had GFR > 90 mL/min and IPI > 1 resulted in a prognostic index that divides patients into 3 prognostic groups (low risk = 0-1, intermediate risk = 2-3 and high risk = 4-5) with an acceptable patient distribution frequency (38%, 39%, and 23%, respectively) and improved statistical significance and separation in comparison to IPI (5-year survival rates of 92%, 74%, and 42%, respectively). GFR is an important independent prognostic factor for B-LCL that should be taken into account in clinical decision making and data analysis and probably be incorporated in prognostic indices.
Blood samples were collected alongside with routine blood cultures (BC) from patients with suspected sepsis, to evaluate the prevalence of different causative agents in patients with bacteraemia. ...Among 667 blood samples, there were 122 positive BC (18%). Haemoglobin content, platelet number, and systolic blood pressure values were significantly lower in patients with positive BC, whereas serum lactate levels, CRP, creatinine and urea content were significantly higher in patients with positive BC. The rate of multidrug (MDR) or extensively drug resistant (XDR) bacteria was 24% (n = 29): Klebsiella pneumoniae (9), Pseudomonas aeruginosa (9), Acinetobacter baumannii (4), Escherichia coli (1), vancomycin resistant Enterococcus spp (VRE) (3), and methicillin-resistant Staphylococcus aureus MRSA (3). The dominant resistance mechanisms were the production of extended-spectrum β-lactamases, OXA-48 carbapenemase, and colistin resistance in K. pneumoniae, VIM metallo-β-lactamases in P. aeruginosa and OXA-23-like oxacillinases in A. baumannii. The study revealed high rate of MDR strains among positive BCs in Zagreb, Croatia.
The extent of protective effects of hemophilia against thrombotic events such as myocardial infarction (MI) and other acute coronary syndromes remains to be determined, as major risk factors for ...cardiovascular disease exist despite factor VIII (FVIII) deficiency. We present a case report of a 41-year-old male with severe hemophilia A and several cardiovascular risk factors.
This morbidly obese patient developed chest pressure, followed by chest pain and difficulty in breathing shortly after receiving on-demand treatment with intravenous recombinant FVIII (rFVIII) (turoctocog alfa) dosed per body weight.
An electrocardiogram revealed a diagnosis of inferior ST-segment elevation MI.
The patient underwent an urgent coronary angiography using a radial artery approach. During the next 12 months, he received dual antiplatelet treatment, acetylsalicylic acid 100 mg, and clopidogrel 75 mg daily. His treatment for severe hemophilia A was changed to plasma-derived FVIII replacement therapy.
During this 12-month period, he experienced several small bleeds in his elbows.
The temporal relationship between rFVIII infusion and onset of the MI suggests a possible association; however, apart from obesity, the patient also had other major risk factors for arterial thrombosis, such as hypertension and smoking. Furthermore, atherosclerotic disease and underlying atherosclerotic changes could not be excluded with certainty. This case highlights the importance of studies assessing the impact of excess body weight on rFVIII dosing.
Disease- and treatment-mediated immunodeficiency might render SARS-CoV-2 vaccines less effective in patients with hematologic diseases. We performed a prospective non-interventional study to evaluate ...humoral response after one and two doses of mRNA-1273, BNT162b2, or ChAdOx1 nCoV-19 vaccine in 118 patients with different malignant or non-malignant hematologic diseases from three Croatian treatment centers. An electrochemiluminescent assay was used to measure total anti-SARS-CoV-2 S-RBD antibody titers. After one vaccine dose, 20/66 (33%) achieved seropositivity with a median antibody titer of 6.1 U/mL. The response rate (58/90, 64.4%) and median antibody titer (>250 U/mL) were higher after two doses. Seropositivity varied with diagnosis (overall p < 0.001), with the lowest rates in lymphoma (34.6%) and chronic lymphocytic leukemia (52.5%). The overall response rate in chronic myeloproliferative neoplasms (CMPN) was 81.3% but reached 100% in chronic myeloid leukemia and other non-myelofibrosis CMPN. At univariable analysis, age > 67 years, non-Hodgkin’s lymphoma, active treatment, and anti-CD20 monoclonal antibody therapy increased the likelihood of no vaccine response, while hematopoietic stem cell recipients were more likely to respond. Age and anti-CD20 monoclonal antibody therapy remained associated with no response in a multivariable model. Patients with the hematologic disease have attenuated responses to SARS-CoV-2 vaccines, and significant variations in different disease subgroups warrant an individualized approach.
To compare the outcomes of Croatian patients with mantle cell lymphoma (MCL) who started treatment in 2007 and 2008 (historical cohort) and of those who started treatment between 2015 and 2017 ...(recent cohort).
The historical cohort consisted of 40 patients who started treatment with rituximab in 2007 and 2008. Data on the recent cohort, consisting of 89 patients, were collected retrospectively from the electronic databases of Croatian hospitals with hematology units. Demographic characteristics and data on induction regimens, autologous stem cell transplantation (ASCT), and rituximab maintenance in the first remission, event-free survival (EFS), and overall survival (OS) were available for both cohorts, and data on cell morphology, mantle cell international prognostic index (MIPI), and Ki67 expression only for the recent cohort.
The recent cohort had significantly better two-year EFS and OS (EFS 58% vs 40%, P=0.014; OS 80% vs 56%, P=0.009), especially in patients below 65. In univariate analysis, induction regimen, ASCT, and maintenance were significant prognostic factors for EFS and the former two for OS. In the multivariate analysis, only ASCT remained significant. Bendamustine+rituximab (BR) induction improved the outcomes of non-transplantable patients over R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, steroid). Blastoid morphology and high MIPI were adverse prognostic factors for EFS and OS.
In the last decade, the outcome of newly diagnosed MCL patients improved. ASCT in the first remission was the main contributor in transplantable patients and BR in non-transplantable. Regularly updated national guidelines may help in a timely adoption of new treatments, thus improving the results.
Urolithiasis may be more prevalent in patients with hemophilia (PWH) than in age-matched non-hemophilic males. We conducted a cross-sectional evaluation of 92 adult PWH at University Hospital Center ...Zagreb. The primary objective was to investigate the frequency of urolithiasis in adult PWH, and the secondary objective was to determine associated risk factors. Urolithiasis was diagnosed by ultrasound and other patient- and hemophilia-related parameters were recorded. The prevalence of urolithiasis was significantly higher among PWH than the reported prevalence in the general Croatian population (10.9% vs 5.9%;
P
= 0.042). Similarly, the incidence of urolithiasis during the course of the disease was significantly higher than the estimated cumulative lifetime incidence of urolithiasis in the Croatian population (25% vs 12%;
P
= 0.001). Multivariate analysis showed that arterial hypertension, the presence of inhibitors, hypercalciuria and hyperbilirubinemia were independent predictors of current urolithiasis (
P
< 0.05), and that hematuria (
P
= 0.051) and prior urinary infections (
P
= 0.059) were also relevant factors.
Urolithiasis is a significant burden in adult PWH. Identifying associated risk factors might help in establishing strategies for earlier recognition and more successful prevention and treatment of urolithiasis.
Although venous thromboembolism (VTE) including deep venous thrombosis (DVT) and pulmonary embolism is a major health problem in the world, it is an infrequent disease among young people. It is ...always mandatory to look at the underlying conditions for VTE, and in young patients, inherited prothrombotic factors should also be evaluated, especially in case of unprovoked VTE. Anomalies of inferior vena cava (IVC) are very rare in the general population. In this case report we describe rare occurrence of extensive DVT in a young male patient with rare anomaly of IVC - duplication of IVC - as a predisposition factor for DVT. Physicians need to be reminded of the IVC anomalies that should be considered in young patients with idiopathic DVT of lower extremity, which may require extended anticoagulant treatment.
Cilj je ovog rada prikaz prvih hrvatskih iskustava pri primjeni eltrombopaga (peroralnog agonista trombopoetinskih receptora), nove opcije u liječenju aplastične anemije (AA).
U ovu retrospektivnu ...analizu uključeni su odrasli bolesnici sa stečenom AA, liječeni eltrombopagom u hrvatskim hematološkim centrima.
Od 2015. do 2019. eltrombopagom je liječeno 13-ero bolesnika s AA (9 žena (69%), medijan dobi 59 (26 – 79) godina): 6-ero ih je imalo tešku aplastičnu anemiju, 6-ero vrlo tešku, a 1 paroksizmalnu noćnu hemoglobinuriju s fenotipom teške AA. Svi su primili eltrombopag nakon prethodne, najmanje jedne linije terapije, i to ili kao monoterapiju ili u kombinaciji s ciklosporinom s niskom dozom metilprednizolona ili bez nje. Hematološki odgovor postiglo je 7-ero (54%) bolesnika: kompletnu remisiju njih četvero, parcijalnu remisiju dvoje, minimalan odgovor jedna bolesnica, a 6-ero (46%) bolesnika bilo je refraktorno. Medijan trajanja primjene eltrombopaga bio je 4 mjeseca (1,5 – 40 mjeseci). Primijenjena srednja doza eltrombopaga bila je 150 mg na dan, a opisane nuspojave bile su u skladu s poznatim podatcima o sigurnosti lijeka. Medijan praćenja iznosio je 16 (2 – 48) mjeseci, a u tom je razdoblju 69% bolesnika i dalje živo. U bolesnice, koja je postigla minimalan odgovor, nakon 8 mjeseci liječenja nastao je relaps AA i razvila se nova citogenska promjena (trisomija 8). Četiri su bolesnika umrla 7 (1 – 12) mjeseci poslije prekida terapije eltrombopagom, i to zbog komorbiditeta i infekcija.
Prikazani podatci iz rutinskoga kliničkog rada hrvatskih hematoloških centara potvrđuju da je eltrombopag zanimljiva nova opcija liječenja odraslih bolesnika sa stečenom teškom AA, posebno onih koji su refraktorni na prethodnu imunosupresivnu terapiju i/ili nisu prikladni za transplantaciju alogenih krvotvornih matičnih stanica.
Anemija uzrokovana manjkom željeza ili sideropenična anemija (SA) važan je javnozdravstveni
problem.
Gotovo 30% čovječanstva (> 2 milijarde) pati od manjka željeza. Posebno su ugroženi predškolska
...djeca, trudnice i žene u generativnoj dobi. Liječenje sideropenične anemije nalaže timski rad jer je važno
pravodobnootkriti
uzrok koji je doveo do gubitka željeza i liječiti anemiju pripravcima željeza. Funkcionalni
manjak željeza jest stanje nedovoljne apsorpcije i fiziološkog iskorištavanja željeza, dok su rezerve željeza očuvane
ili čak povećane. Ovaj poremećaj tipičan je za anemiju kod kronične bolesti, kronične upalne bolesti, kroničnoga
srčanog popuštanja i maligne bolesti. Pri liječenju sideropenične anemije rabimo oralne i parenteralne pripravke
željeza. Noviji parenteralni pripravci daju se u visokoj dozi (jedna ili dvije aplikacije), veoma su djelotvorni i sigurni
za primjenu.
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